Adenocarcinomas of the gastro-oesophageal junction : from gene to clinic

Adenocarcinomas of the gastro-oesophageal junction are thought to arise from premalignant Barretr's epithelium. Barrett's epithelium is columnar epithelium that has replaced the normal squamous cell lining of the oesopha",ous. This metaplastic change is driven by duodeno-gastro-oesophageal reflu.'(, which leads to oesophagitis and ultimately, in some patients, to Barrett's epithelium. The development of Barrett's carcinoma involves multiple genetic changes. In PART I, the general introduction of this thesis, CHAPTER 1 reviews our current knowledge on these genetic changes involved in the progression from Barrett's oesophagus to adenocarcinoma. Over the past decades, many researchers focused on the role of cell-cell adhesion in carcinogenesis. The E-cadherin-catenin complex is thought to be the most important regulator of tight cell-cell adhesion in normal tissues, and perturbation of this complex is associated with malignancy. There is evidence that dysfunction of the E-cadherin-catenin complex also plays an important role in the pathogenesis of adenocarcinomas of the gastro-oesophageal junction. In CHAPTER 2, the literature on the role of the E-cadherin-catenin complex in human cancer and the possible clinical implications are discussed. This chapter serves as an introduction to Part IV (chapters 7-10). PART II of the thesis deals ",~th epidemiological and clinical aspects of adenocarcinomas of the gastro-oesophageal junction